PROJECT SUMMARY Paralysis following spinal cord injury is a devastating condition for which there is no adequate treatment. The injury disrupts motor and sensory communication between the brain and body. Re-establishing communication with a brain-machine interface (BMI) remains one of the most promising treatment strategies. A BMI establishes connections between (1) recorded brain signals and a device, e.g. a robotic hand, to provide motor output and (2) external sensors, e.g. of grasp force, and brain stimulation to provide sensory feedback. Recently, two independent studies have demonstrated that it is possible to reanimate an individual's own paralyzed hand, using brain-controlled muscle stimulation, instead of relying on a robotic device. This major advance provides a clear pathway toward naturalistic restoration of motor function after paralysis. However, the critical issue of how to provide a sense of touch for reanimated paralyzed hands has not been addressed. Ideally, tactile sensors for a reanimated human hand should be transparent to the user: implanted devices free from the constraints of gloves or wires. Previous tactile sensors for BMIs have been designed for robotic hands, where issues of size, power, and data transmission are less constrained. Thus, new technology is needed. In this project, we will develop an implantable, wireless tactile feedback system designed specifically for the human hand. First, we aim to develop a miniature, silica-based hermetic package with a built-in network of capacitors sensitive to normal and shear forces over a physiological range. Second, we aim to design an application-specific integrated circuit (ASIC) to be housed inside the implantable package to process the sensor capacitance changes and wirelessly transmit the data to a battery-powered base unit worn on the wrist. The base unit will also remotely power the ASIC through magnetic resonance at MHz frequencies, using the body as a communication channel. Third, we aim to test the complete, wireless sensor system in the non- human primate hand. The sensitive and stability of the implanted sensor output will be quantified and its function in the presence of simultaneous muscle stimulation assessed. This project leverages a strong collaboration between investigators with expertise in surgery, neuroengineering, microelectromechanical systems, low-power sensor electronics, and radiofrequency integrated circuits. The microfabricated sensor, hermetic packaging, wireless powering, and wireless read-out technology will provide important advances to the field of implantable medical devices. Ultimately, the sensor system could be combined with brain-controlled muscle stimulation to provide closed-loop hand reanimation in paralyzed subjects, with large expected gains in performance. The addition of tactile feedback to reanimation strategies would be a substantial step towards a clinical BMI allowing the thousands of newly paralyzed individuals each year to regain functional independence.